Correlation of Annealing with Chemical Stability in Lyophilized Pharmaceutical Glasses

Abstract

This research constitutes a thorough study of the relationship between the chemical stability, aging state and global molecular motion on the one hand, and microscopic local mobility in multi‐component systems on the other hand. The objective of the present work was to determine whether annealing a glass below T_g affects its chemical stability and determine if the rate of chemical degradation couples with global relaxation times determined using calorimetery, and/or with T₁ and T_1rho relaxation times measured using ssNMR. Model compounds chosen for this research were lyophilized aspartame/sucrose and aspartame/trehalose (1:10 w/w) formulations. The chemical degradation was assessed at various temperatures using high‐performance liquid chromatography (HPLC) to determine the impact of annealing on chemical stability. The rate constant for chemical degradation was estimated using stretched time kinetics. The results support the hypothesis that thermal history affects the molecular mobility required for structural relaxation and such effect is critical for chemical stability, that is, a stabilization effect upon annealing is observed. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5240–5251, 2008